TY - JOUR
T1 - Microdeletion 9q22.3 syndrome includes metopic craniosynostosis, hydrocephalus, macrosomia, and developmental delay
AU - Muller, Eric A.
AU - Aradhya, Swaroop
AU - Atkin, Joan F.
AU - Carmany, Erin P.
AU - Elliott, Alison M.
AU - Chudley, Albert E.
AU - Clark, Robin D.
AU - Everman, David B.
AU - Garner, Shannon
AU - Hall, Bryan D.
AU - Herman, Gail E.
AU - Kivuva, Emma
AU - Ramanathan, Subhadra
AU - Stevenson, David A.
AU - Stockton, David W.
AU - Hudgins, Louanne
PY - 2012/2
Y1 - 2012/2
N2 - Basal cell nevus syndrome (BCNS), also known as Gorlin syndrome (OMIM #109400) is a well-described rare autosomal dominant condition due to haploinsufficiency of PTCH1. With the availability of comparative genomic hybridization arrays, increasing numbers of individuals with microdeletions involving this locus are being identified. We present 10 previously unreported individuals with 9q22.3 deletions that include PTCH1. While 7 of the 10 patients (7 females, 3 males) did not meet strict clinical criteria for BCNS at the time of molecular diagnosis, almost all of the patients were too young to exhibit many of the diagnostic features. A number of the patients exhibited metopic craniosynostosis, severe obstructive hydrocephalus, and macrosomia, which are not typically observed in BCNS. All individuals older than a few months of age also had developmental delays and/or intellectual disability. Only facial features typical of BCNS, except in those with prominent midforeheads secondary to metopic craniosynostosis, were shared among the 10 patients. The deletions in these individuals ranged from 352kb to 20.5Mb in size, the largest spanning 9q21.33 through 9q31.2. There was significant overlap of the deleted segments among most of the patients. The smallest common regions shared among the deletions were identified in order to localize putative candidate genes that are potentially responsible for each of the non-BCNS features. These were a 929kb region for metopic craniosynostosis, a 1.08Mb region for obstructive hydrocephalus, and a 1.84Mb region for macrosomia. Additional studies are needed to further characterize the candidate genes within these regions.
AB - Basal cell nevus syndrome (BCNS), also known as Gorlin syndrome (OMIM #109400) is a well-described rare autosomal dominant condition due to haploinsufficiency of PTCH1. With the availability of comparative genomic hybridization arrays, increasing numbers of individuals with microdeletions involving this locus are being identified. We present 10 previously unreported individuals with 9q22.3 deletions that include PTCH1. While 7 of the 10 patients (7 females, 3 males) did not meet strict clinical criteria for BCNS at the time of molecular diagnosis, almost all of the patients were too young to exhibit many of the diagnostic features. A number of the patients exhibited metopic craniosynostosis, severe obstructive hydrocephalus, and macrosomia, which are not typically observed in BCNS. All individuals older than a few months of age also had developmental delays and/or intellectual disability. Only facial features typical of BCNS, except in those with prominent midforeheads secondary to metopic craniosynostosis, were shared among the 10 patients. The deletions in these individuals ranged from 352kb to 20.5Mb in size, the largest spanning 9q21.33 through 9q31.2. There was significant overlap of the deleted segments among most of the patients. The smallest common regions shared among the deletions were identified in order to localize putative candidate genes that are potentially responsible for each of the non-BCNS features. These were a 929kb region for metopic craniosynostosis, a 1.08Mb region for obstructive hydrocephalus, and a 1.84Mb region for macrosomia. Additional studies are needed to further characterize the candidate genes within these regions.
KW - 9q22
KW - Basal cell carcinoma syndrome
KW - Basal cell nevus syndrome
KW - Chromosomal deletion
KW - Gorlin syndrome
KW - Metopic craniosynostosis
KW - PTCH1
UR - http://www.scopus.com/inward/record.url?scp=84856228759&partnerID=8YFLogxK
U2 - 10.1002/ajmg.a.34216
DO - 10.1002/ajmg.a.34216
M3 - Article
C2 - 22190277
AN - SCOPUS:84856228759
VL - 158 A
SP - 391
EP - 399
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
SN - 1552-4825
IS - 2
ER -